This project investigates the environmental and physiological regulation of the pineal gland, exclusive of transmembrane and intracellular regulatory mechanisms (see ZOI HD 00095-20 LDN). The pineal gland is part of the melatonin rhythm generating system a neural circuit which includes a circadian clock in the suprachiasmatic nucleus (SCN); the SCN is reset and entrained by light acting through the eve. Several new areas of research have been initiated in this program within the past year. One involves Na+,K+ -ATPase. It has been discovered that the pineal contains three subtypes of this enzyme. Analysis of neural and photic regulation of the levels of these enzymes has revealed that one of the high affinity forms of the enzyme is selectively depressed following surgical denervation of the gland. This may reflect either a neuronal localization of this form of the enzyme, or the existence of a neural mechanism which regulates levels of this enzyme. Another area of interest is proteins involved in transmembrane signal processing. These include G proteins, MEKA and the S-antigen. These studies indicate that MEKA and the S-antigen are absent before birth and appear rapidly during the first postnatal week in the rat. In contrast, G beta is present at adult levels prior to birth. In the adult, it has been found that the amount of MEKA and the phosphorylation state of this enzyme are regulated by environmental lighting. Total MEKA increases at night; phosphorylation also increases at night in the dark and the protein is rapidly dephosphorylated by exposure to light.